Tγδ LGLL identifies a subset with more symptomatic disease: analysis of an international cohort of 137 patients

• Published in: Blood Vol. 141; no. 9; pp. 1036 - 1046
• Main Authors: Barilà, Gregorio, Grassi, Angela, Cheon, HeeJin, Teramo, Antonella, Calabretto, Giulia, Chahal, Jasmanet, Vicenzetto, Cristina, Almeida, Julia, Shemo, Bryna C., Shi, Min, Gasparini, Vanessa Rebecca, Munoz-Garcia, Noemi, Pastoret, Cédric, Nakazawa, Hideyuki, Oshimi, Kazuo, Sokol, Lubomir, Ishida, Fumihiro, Lamy, Thierry, Orfao, Alberto, Morice, William G., Loughran, Thomas P., Semenzato, Gianpietro, Zambello, Renato
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.03.2023; The American Society of Hematology
• Subjects: Humans; Leukemia, Large Granular Lymphocytic - genetics; Lymphoid Neoplasia; Mutation; Neutropenia - genetics; Retrospective Studies
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2021013489

•STAT3 mutations and Vδ2 status are needed to properly stratify Tγδ LGLL patients.•Independently from STAT3 mutations, Tγδ LGLL represents a subset of T-LGLL characterized by dismal outcome as compared with Tαβ LGLL. [Display omitted] Tγδ large granular lymphocyte leukemia (LGLL) is a rare variant of T-cell LGLL (T-LGLL) that has been less investigated as compared with the more frequent Tαβ LGLL, particularly in terms of frequency of STAT3 and STAT5b mutations. In this study, we characterized the clinical and biological features of 137 patients affected by Tγδ LGLL; data were retrospectively collected from 1997 to 2020 at 8 referral centers. Neutropenia and anemia were the most relevant clinical features, being present in 54.2% and 49.6% of cases, respectively, including severe neutropenia and anemia in ∼20% of cases each. Among the various treatments, cyclosporine A was shown to provide the best response rates. DNA samples of 97 and 94 cases were available for STAT3 and STAT5b mutation analysis, with 38.1% and 4.2% of cases being mutated, respectively. Clinical and biological features of our series of Tγδ cases were also compared with a recently published Tαβ cohort including 129 cases. Though no differences in STAT3 and STAT5b mutational frequency were found, Tγδ cases more frequently presented with neutropenia (P = .0161), anemia (P < .0001), severe anemia (P = .0065), and thrombocytopenia (P = .0187). Moreover, Vδ2− cases displayed higher frequency of symptomatic disease. Overall, Tγδ cases displayed reduced survival with respect to Tαβ cases (P = .0017). Although there was no difference in STAT3 mutation frequency, our results showed that Tγδ LGLL represents a subset of T-LGLL characterized by more frequent symptoms and reduced survival as compared with Tαβ LGLL. Large granular lymphocyte leukemia (LGLL) is most commonly Tαβ LGLL in type. LGLL associated with γδ T cells (Tγδ LGLL) is less studied and had previously been reported to have a similar natural history and prognosis. Barilà et al present a multicenter retrospective review of 137 patients with Tγδ LGLL, reporting that they have the same prevalence of STAT3 mutations but are more frequently symptomatic, largely from cytopenias, respond best to cyclosporine A, and have reduced survival compared to Tαβ LGLL.